{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T15:59:52Z","timestamp":1784735992771,"version":"3.55.0"},"reference-count":53,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T00:00:00Z","timestamp":1648771200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Cent Nerv Syst Dis"],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:p>The high efficacy of natalizumab in the treatment of relapsing-remitting multiple sclerosis (MS) is without controversy. Indeed, effective disease control was not only demonstrated in the pivotal trials but has been corroborated impressively in real-world observations. This monoclonal IgG4 antibody blocks the \u03b14\u03b21 integrin-mediated leukocyte-endothelial interaction and thereby inhibits the migration of immune cells to the brain parenchyma. However, treatment with natalizumab carries the risk of progressive multifocal leukoencephalopathy (PML). This potentially lethal side effect is a significant limitation for treatment initiation and long-term therapy. Natalizumab is given intravenously or subcutaneously in the standard dose of 300\u00a0mg every 4\u00a0weeks, allowing drug concentrations at levels that ensure continuous \u03b14\u03b21 integrin receptor saturation on the surface of immune cells. Extended-interval dosing (EID) is an emerging treatment approach that aims to mitigate the natalizumab-related PML risk by prolonging the standard infusion intervals to 6\u00a0weeks or even more. This treatment approach may abrogate the PML risk due to improved immune surveillance within the central nervous system while maintaining clinical efficacy. Moreover, even an individual interval dosing can be envisioned based on the availability of a biomarker that is capable of monitoring both safety and efficacy aspects. This review summarizes the early and encouraging evidence for EID from observational and randomized-controlled trials and discusses current limitations and upcoming challenges for introducing a tailored treatment approach.<\/jats:p>","DOI":"10.1177\/11795735221135485","type":"journal-article","created":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T14:18:35Z","timestamp":1666016315000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":7,"title":["Natalizumab extended-interval dosing in multiple sclerosis to mitigate progressive multifocal leukoencephalopathy risk: initial study evidence and real-world experience"],"prefix":"10.1177","volume":"14","author":[{"given":"Julian","family":"Perneczky","sequence":"first","affiliation":[{"name":"Department of Neurology, Landesklinikum Mistelbach-G\u00e4nserndorf, Mistelbach, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8749-5533","authenticated-orcid":false,"given":"Johann","family":"Sellner","sequence":"additional","affiliation":[{"name":"Department of Neurology, Landesklinikum Mistelbach-G\u00e4nserndorf, Mistelbach, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2022,10,17]]},"reference":[{"key":"bibr1-11795735221135485","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1401483"},{"key":"bibr2-11795735221135485","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2020.11.022"},{"key":"bibr3-11795735221135485","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20858"},{"key":"bibr4-11795735221135485","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01564"},{"key":"bibr5-11795735221135485","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa044396"},{"key":"bibr6-11795735221135485","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa044397"},{"key":"bibr7-11795735221135485","doi-asserted-by":"publisher","DOI":"10.1177\/13524585211065711"},{"key":"bibr8-11795735221135485","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurol.2021.02.393"},{"key":"bibr9-11795735221135485","doi-asserted-by":"publisher","DOI":"10.1177\/13524585211003020"},{"key":"bibr10-11795735221135485","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.707"},{"key":"bibr11-11795735221135485","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a029066"},{"key":"bibr12-11795735221135485","doi-asserted-by":"publisher","DOI":"10.1177\/2055217316630008"},{"key":"bibr13-11795735221135485","doi-asserted-by":"publisher","DOI":"10.1177\/11795735211042188"},{"key":"bibr14-11795735221135485","doi-asserted-by":"publisher","DOI":"10.4137\/JCNSD.S14049"},{"key":"bibr15-11795735221135485","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26198"},{"key":"bibr16-11795735221135485","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(17)30282-X"},{"key":"bibr17-11795735221135485","doi-asserted-by":"publisher","DOI":"10.1007\/s13365-016-0427-6"},{"key":"bibr18-11795735221135485","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.51130"},{"key":"bibr19-11795735221135485","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2018.09.012"},{"key":"bibr20-11795735221135485","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa020696"},{"key":"bibr21-11795735221135485","doi-asserted-by":"publisher","DOI":"10.1586\/14737175.4.4.571"},{"key":"bibr22-11795735221135485","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2021.716548"},{"key":"bibr23-11795735221135485","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1737"},{"key":"bibr24-11795735221135485","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2019.03.017"},{"key":"bibr25-11795735221135485","doi-asserted-by":"publisher","DOI":"10.1186\/2051-5960-2-27"},{"key":"bibr26-11795735221135485","unstructured":"https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/tysabri-epar-product-information_en.pdf version of 04\/05\/2020."},{"key":"bibr27-11795735221135485","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-016-0635-2"},{"key":"bibr28-11795735221135485","doi-asserted-by":"publisher","DOI":"10.1111\/ane.12182"},{"key":"bibr29-11795735221135485","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000000672"},{"key":"bibr30-11795735221135485","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000008243"},{"key":"bibr31-11795735221135485","unstructured":"Clinicaltrials.org. 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